In mid-December 2017, the U.S. Food and Drug Administration (FDA)released a guidance framework for how researchers should approach gene therapy, in terms of development and regulatory approval. This was initiated on the first-ever approval of a gene therapy for a disease caused by mutations in a specific gene. The therapy was for Spark Therapeutics’ Luxturna (voretigene neparvovec-rzyl) to treat an inherited retinal disease caused by mutations to both copies of the RPE65 gene.

On June 11, 2018, FDA Commissioner Scott Gottliebreleased a complementary framework for gene therapies, noting that in the last 12 months the agency has approved three different gene therapy products. “This reflects the rapid advancements in this field,” Gottlieb stated. “An inflection point was reached with the development of vectors that could reliably deliver gene cassettes in vivo, into cells and human tissue. In the future, we expect this field to continue to expand, with the potential approval of new treatments for many debilitating diseases. These therapies hold great promise. Our new steps are aimed at fostering developments in this innovative field.”

Gottlieb also notes that, compared to more traditional therapies, gene therapies have specific challenges, particularly related to durability of response. “We know that we still have much to learn about how these products work, how to administer them safely, and whether they will continue to work properly in the body without causing adverse side effects over long periods of time. In contrast to traditional drug review, some of the more challenging questions when it comes to gene therapy relate to product manufacturing and quality, or questions about the durability of response, which often can’t be fully answered in any reasonably sized pre-market trial.”

In fact, he goes on to say that at approval, it’s not always possible to understand the long-term durability of a gene therapy, which may require significant post-market follow up and trials.

The additional guidance framework consists of six scientific documents that can be used as building blocks for developing and getting approval for gene therapies. Three are for specific disease categories: hemophilia, retinal disorders and rare diseases. The other three update topics related to manufacturing.

The agency encourages feedback during the comment period. Once they are finalized, they will replace previous guidelines the FDA issued in April 2008 (CMC) and November 2006 (RCR and LTFU).

Gottlieb stated, “Our goal is to help promote safe and effective product development in this field. We’ll continue to work with the product sponsors to help make the development and approval of these innovative gene therapies more efficient, while putting in place the regulatory controls needed to ensure that the resulting therapies are both safe and effective. We’ll also make full use of our expedited programs such as breakthrough therapy designation and regenerative medicine advanced therapy designation whenever possible.”